One of the greatest challenges in drug delivery systems is the controlled delivery of protein based drugs due to their short half-life in the circulatory system, low permeability, rapid proteolysis (low stability) and immunogenicity. The use of multiple unit dosage forms, such as polymeric microspheres, greatly reduces absorption differences in patients compared to where single unit dosage forms such as tablets are administered and provides more efficient drug accumulation at target sites in the human body. Many techniques have been proposed for preparation of polymeric microspheres for drug administration. The most commonly used reported techniques involve solvent evaporation or multiple emulsion solvent evaporation. These techniques rely on organic solvents which cause decrease in bioactivity in protein-based drugs and which are generally toxic and therefore require total removal.
The overall survival of patients with oral cancer has remained at about 50% for the last four decades. Cytokine immunotherapy has shown encouraging results in animal models and early clinical tests. However, when cytokines are administered systemically, they exhibit a formidable toxicity profile. While local sustained release of proinflammatory cytokines into tumor microenvironment would be possible by release from hydrogels, loading of known hydrogels with cytokines has required loading from organic solution of cytokine and this results in significant loss of cytokine bioactivity.
Thus there is a need for polymeric microsphere dosage forms which can be formed without the need for use of organic solvents and which will load water soluble protein drugs without inactivation of the drugs.